The long term goal of this proposal is to determine the role of polypeptide growth factors in the regulation of endothelial cell migration, proliferation and differentiation. Multiple forms of endothelial cell growth factor (ECGF) have been identified and their primary structures elucidated. Similarly multiple functions are indicated for this family of polypeptides. The specific aims of the proposal are (1) to characterize the functional domains of ECGF and to correlate these domains with structural domains of the polypeptides; (2) to determine the extent to which structural features that are common to both ECGF and basic fibroblast growth factor (FGF) reflect common functions; (3) to determine whether acidic FGF and alpha-ECGF result from post- translational processing of beta-ECGF and (4) to extend our data on the human ECGF cDNA sequence to include analysis of the structure of the gene encoding ECGF and to compare its structure to that of the gene for basic-FGF. These studies will provide a structural basis for establishing the mechanism of action of factors that modulate endothelial cell growth and differentiation such as heparin. In addition, it is anticipated that these studies will result in the identification of specific peptidic and immunological modulators of endothelial cell growth and migration. The availability of such modulators should have a significant impact on studies of atherosclerosis, wound healing and other hemostatic or pathophysiological processes involving the vascular wall. The studies will involve testing the ability of enzymatic or chemically derived fragments of ECGF to either mimic or inhibit the mitogenic and chemotactic activities of the intact polypeptide. Site specific and site directed antibodies of ECGF will be generated and characterized as modulators of ECGF action. Comparative functional studies with basis FGF will be completed and the genes for ECGF and basic-FGF will be studied to determine the evolutionary relationships and the pre-pro relationships of the isolated polypeptides.